Alzheimer's Disease : Current Landscape and Future Directions
DOI:
https://doi.org/10.32628/IJSRST24115100Keywords:
Monoclonal Antibodies, Anti-Amyloids, Blood Based Biomarkers, Conventional & Novel TreatmentAbstract
Introduction: Alzheimer's disease (AD) is the most prevalent form of dementia, constituting up to 72% of cases, and poses a significant financial burden on global healthcare. The aging population is expected to triple the cost of dementia to over $600 billion in the US alone by 2050. Dementia, a major cause of dependency and dysfunction, accounted for 11.4% of all reported deaths in Britain and Wales in 2022. Recent studies suggest a potential decline in dementia incidence, especially in males in Occident countries, possibly linked to better management of vascular risk. While 89% of dementia costs are attributed to high-income countries, middle and low-income nations face significant challenges in addressing the epidemiology of dementia. The prevalence of AD in developing nations is estimated at 3.4%, varying widely. Women exhibit a 1.17 times higher age-specific global prevalence compared to men, and their age-normalized death rate is also higher, suggesting factors beyond life expectancy contribute to their vulnerability. AD primarily affects individuals aged 75 or older, with 80% of cases in this age group. Acetylcholinesterase inhibitors are commonly used in all stages of dementia, though their efficacy in mild cognitive impairment and prodromal AD is uncertain. Distinguishing AD from depression symptoms can be challenging. The pathological features of AD involve neurofibrillary tangles (NFTs) and senile plaques, leading to neural and synaptic loss. Multiple mechanisms contribute to AD pathogenesis, including amyloid/tau toxicity and oxidative stress. Diagnosis : traditionally relies on clinical criteria, but biomarkers like CSF Aβ and tau proteins, as well as blood-based biomarkers, have shown promise in early detection. Noveltrearment: Promising treatment options include anti-amyloid monoclonal antibodies like aducanumab, lecanemab, and gantenerumab, with varying degrees of success in clinical trials. Donanemab, targeting a specific type of Aβ, has shown significant slowing of mental degradation in early-stage patients.
Downloads
References
Bhushan, I., Kour, M., Kour, G., Gupta, S., Sharma, S., & Yadav, A. (2018). Alzheimer’s disease: Causes & treatment–A review. Ann Biotechnol, 1(1), 1002. DOI: https://doi.org/10.33582/2637-4927/1002
Livingston, G.; Huntley, J.; Sommerlad, A.; Ames, D.; Ballard, C.; Banerjee, S.; Brayne, C.; Burns, A.; Cohen-Mansfield, J.; Cooper, C.; et al. Dementia Prevention, Intervention, and Care: 2020 Report of the Lancet Commission. Lancet 2020, 396, 413–446. DOI: https://doi.org/10.1016/S0140-6736(20)30367-6
Prince M, Albanese E, Guerchet M, et al. World Alzheimer Report 2014: Dementia and Risk Reduction an Analysis of Protective and Modifiable Factors, 2014.
Office of National Statistics. Deaths Registered in England and Wales, 2016; 1– 15.
Wu Y-T, Fratiglioni L, Matthews FE, et al. Dementia in western Europe: epidemiological evidence and implications for policy making. Lancet Neurol 2016; 15: 116– 124. DOI: https://doi.org/10.1016/S1474-4422(15)00092-7
Llibre Rodriguez JJ, Ferri CP, Acosta D, et al. Prevalence of dementia in Latin America, India, and China: a population-based cross-sectional survey. Lancet. 2008;372:464-474 DOI: https://doi.org/10.1016/S0140-6736(08)61002-8
Global, regional, and national burden of Alzheimer’s disease and other dementias, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. The Lancet. Neurology 2019;18: 88-106.
Hafez Ghoran, S., & Kijjoa, A. (2021). Marine-derived compounds with anti-Alzheimer’s disease activities. Marine Drugs, 19(8), 410.
Silva, M., Seijas, P., & Otero, P. (2021). The exploitation of marine molecules to manage Alzheimer’s disease. Marine Drugs, 19(7), 373 DOI: https://doi.org/10.3390/md19070373
Zhang, X. X., Tian, Y., Wang, Z. T., Ma, Y. H., Tan, L., & Yu, J. T. (2021). The epidemiology of Alzheimer’s disease modifiable risk factors and prevention. The journal of Prevention of Alzheimer's Disease, 8, 313-321 DOI: https://doi.org/10.14283/jpad.2021.15
Ossenkoppele, R.; van der Kant, R.; Hansson, O. Tau Biomarkers in Alzheimer’s Disease: Towards Implementation in Clinical Practice and Trials. Lancet Neurol. 2022, 21, 726–734. DOI: https://doi.org/10.1016/S1474-4422(22)00168-5
Joe, E., & Ringman, J. M. (2019). Cognitive symptoms of Alzheimer’s disease: clinical management and prevention. BMJ, 367. DOI: https://doi.org/10.1136/bmj.l6217
Perez Ortiz, J.M.; Swerdlow, R.H. Mitochondrial dysfunction in Alzheimer’s disease: Role in pathogenesis and novel therapeutic opportunities. Br. J. Pharmacol.2019, 176, 3489–3507 DOI: https://doi.org/10.1111/bph.14585
Thies W and Bleiler L Alzheimer’s disease facts and figures. AlAlzheimer Dement.2
Takeda, S., Sato, N., & Morishita, R. (2014). Systemic inflammation, blood-brain barrier vulnerability and cognitive/non-cognitive symptoms in Alzheimer disease: relevance to pathogenesis and therapy. Frontiers in aging neuroscience, 6, 171. DOI: https://doi.org/10.3389/fnagi.2014.00171
Small, G.W. Updates in the Management of Mild Cognitive Impairment and Alzheimer Disease. J. Fam. Pract. 2022, 71, S82–S87. ] DOI: https://doi.org/10.12788/jfp.0374
Kumar A, Singh A, Ekavali. A review on Alzheimer’s disease pathophysiology and its management: an update. Pharmacol Rep. 2015;67(2):195–203. DOI: https://doi.org/10.1016/j.pharep.2014.09.004
Ju, Y.; Tam, K. Pathological Mechanisms and Therapeutic Strategies for Alzheimer’s Disease. Neural Regen. Res. 2022, 17, 543. DOI: https://doi.org/10.4103/1673-5374.320970
Jellinger, K.A. Recent Update on the Heterogeneity of the Alzheimer’s Disease Spectrum. J. Neural Transm. 2022, 129, 1–24. DOI: https://doi.org/10.1007/s00702-021-02449-2
D.R.; Capetillo-Zarate, E.; Del Tredici, K.; Braak, H. The Development of Amyloid Beta Protein Deposits in the Aged Brain. Sci. Aging Knowl. Environ. 2006, 2006, DOI: https://doi.org/10.1126/sageke.2006.6.re1
Hojjati, S.H.; Feiz, F.; Ozoria, S.; Razlighi, Q.R. Alzheimer’s Disease Neuroimaging Initiative Topographical Overlapping of the Amyloid-β and Tau Pathologies in the Default Mode Network Predicts Alzheimer’s Disease with Higher Specificity. J. Alzheimers Dis. JAD 2021, 83, 407–421. DOI: https://doi.org/10.3233/JAD-210419
Thakur, A. K., Kamboj, P., Goswami, K., & Ahuja, K. J. J. A. P. R. (2018). Pathophysiology and management of Alzheimer’s disease: An overview. J. Anal. Pharm. Res, 7(1). DOI: https://doi.org/10.15406/japlr.2018.07.00230
McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging−Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7:263-269. DOI: https://doi.org/10.1016/j.jalz.2011.03.005
van der Schaar, J.; Visser, L.N.C.; Bouwman, F.H.; Ket, J.C.F.; Scheltens, P.; Bredenoord, A.L.; van der Flier, W.M. Considerations Regarding a Diagnosis of Alzheimer’s Disease before Dementia: A Systematic Review. Alzheimers Res. Ther. 2022, 14, 31. DOI: https://doi.org/10.1186/s13195-022-00971-3
Davenport, F.; Gallacher, J.; Kourtzi, Z.; Koychev, I.; Matthews, P.M.; Oxtoby, N.P.; Parkes, L.M.; Priesemann, V.; Rowe, J.B.; Smye, S.W.; et al. Neurodegenerative Disease of the Brain: A Survey of Interdisciplinary Approaches. J. R. Soc. Interface 2023, 20, 20220406. DOI: https://doi.org/10.1098/rsif.2022.0406
Zhou, Y.; Song, Z.; Han, X.; Li, H.; Tang, X. Prediction of Alzheimer’s Disease Progression Based on Magnetic Resonance Imaging. ACS Chem. Neurosci. 2021, 12, 4209–4223. DOI: https://doi.org/10.1021/acschemneuro.1c00472
Jack CR Jr, Bennett DA, Blennow K, et al. NIA-AA research framework: toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018;14:535-562. DOI: https://doi.org/10.1016/j.jalz.2018.02.018
Martins, A.; Vieira, H.; Gaspar, H.; Santos, S. Marketed Marine Natural Products in the Pharmaceutical and Cosmeceutical Industries: Tips for Success. Mar. Drugs 2014, 12, 1066–1101. DOI: https://doi.org/10.3390/md12021066
Lindequist, U. Marine-derived pharmaceuticals—Challenges and opportunities. Biomol. Ther. 2016, 24, 561–571. DOI: https://doi.org/10.4062/biomolther.2016.181
Malve, H. Exploring the ocean for new drug developments: Marine pharmacology. J. Pharm. Bioallied Sci. 2016, 8, 83–91. DOI: https://doi.org/10.4103/0975-7406.171700
Bahbah, E.I.; Ghozy, S.; Attia, M.S.; Negida, A.; Emran, T.B.; Mitra, S. Albadrani, G.M.; Abdel-Daim, M.M.; Uddin, M.S.; Simal-Gandara, J. Molecular Mechanisms of Astaxanthin as a Potential Neurotherapeutic Agent. Mar. Drugs 2021, 19, 201. DOI: https://doi.org/10.3390/md19040201
Kabir, M.T.; Uddin, M.S.; Jeandet, P.; Emran, T.B.; Mitra, S.; Albadrani, G.M.; Sayed, A.A.; Abdel-Daim, M.M.; Simal-Gandara, J. Anti-Alzheimer’s molecules derived from marine life: Understanding molecular mechanisms and therapeutic potential. Mar. Drugs 2021, 19, 251.
Russo, P.; Kisialiou, A.; Lamonaca, P.; Moroni, R.; Prinzi, G.; Fini, M. New drugs from marine organisms in Alzheimer’s disease. Mar. Drugs 2016, 14, 5. DOI: https://doi.org/10.3390/md14010005
Lakshmi, S.; Prakash, P.; Essa, M.M.; Qoronfleh, W.M.; Akbar, M.; Song, B.J.; Kumar, S.; Elimali, P. Marine derived bioactive compounds for treatment of Alzheimer’s disease. Front. Biosci. 2018, 10, 537–548. DOI: https://doi.org/10.2741/e840
Ghoran, S.H.; Kijjoa, A. Marine-derived compounds with anti-Alzheimer’s disease activities. Mar. Drugs 2021, 19, 410. DOI: https://doi.org/10.3390/md19080410
Rahman, M.A.; Dash, R.; Sohag, A.A.M.S.; Alam, M.; Rhim, H.; Ha, H.; Moon,I.S.; Uddin, M.J.; Hannan, M.A. Prospects of marine sterols against pathobiology of Alzheimer’s disease: Pharmacological insights and technological advances. Mar. Drugs 2021, 19, 167. DOI: https://doi.org/10.3390/md19030167
Lima, E.; Medeiros, J. Marine Organisms as Alkaloid Biosynthesizers of Potential Anti-Alzheimer Agents. Mar. Drugs 2022, 20, 75. [Google Scholar][CrossRef]
Bălasa, A.F.; Chircov, C.; Grumezescu, A.M. Marine Biocompounds for Neuroprotection—A Review. Mar. Drugs 2020, 18, 290 DOI: https://doi.org/10.3390/md18060290
Hu, D.; Jin, Y.; Hou, X.; Zhu, Y.; Chen, D.; Tai, J.; Chen, Q.; Shi, C.; Ye, J.; Wu, M.; et al. Application of Marine Natural Products against Alzheimer’s Disease: Past, Present and Future. Mar. Drugs 2023, 21, 43. DOI: https://doi.org/10.3390/md21010043
Karthikeyan, A.; Joseph, A.; Nair, B.G. Promising bioactive compounds from the marine environment and their potential effects on various diseases. J. Genet. Eng. Biotechnol. 2022, 20, 14. DOI: https://doi.org/10.1186/s43141-021-00290-4
Kabir, M.T.; Uddin, M.S.; Jeandet, P.; Emran, T.B.; Mitra, S.; Albadrani, G.M.; Sayed, A.A.; Abdel-Daim, M.M.; Simal-Gandara, J. Anti-Alzheimer’s molecules derived from marine life: Understanding molecular mechanisms and therapeutic potential. Mar. Drugs 2021, 1 DOI: https://doi.org/10.3390/md19050251
Lima, E.; Medeiros, J. Marine Organisms as Alkaloid Biosynthesizers of Potential Anti-Alzheimer Agents. Mar. Drugs 2022, 20, 75. DOI: https://doi.org/10.3390/md20010075
Habtemariam, S. Natural products in Alzheimer’s disease therapy: Would old therapeutic approaches fix the broken promise of modern medicines? Molecules 2019, 24, 1519. DOI: https://doi.org/10.3390/molecules24081519
Chen, X.; Drew, J.; Berney, W.; Lei, W. Neuroprotective natural products for Alzheimer’s disease. Cells 2021, 10, 1309. DOI: https://doi.org/10.3390/cells10061309
Patil, P., Kataria, B., Redkar, V., Banait, A., Shilpa, C., Patil, & Khetani, V. (08 2024). Automated Detection of Tuberculosis Using Deep Learning Algorithms on Chest X-rays. Frontiers in Health Informatics, 13, 218–229. https://healthinformaticsjournal.com/index.php/IJMI/article/view/20
Bhavesh Kataria, "The Challenges of Utilizing Information Communication Technologies (ICTs) in Agriculture Extension, International Journal of Scientific Research in Science, Engineering and Technology, Print ISSN : 2395-1990, Online ISSN : 2394-4099, Volume 1, Issue 1, pp.380-384, January-February-2015. Available at : https://doi.org/10.32628/ijsrset1511103 DOI: https://doi.org/10.32628/IJSRSET1511103
Noori, T.; Dehpour, A.R.; Sureda, A.; Sobarzo-Sanchez, E.; Shirooie, S. Role of natural products for the treatment of Alzheimer’s disease. Eur. J.Pharmacol. 2021, 898, 173974. DOI: https://doi.org/10.1016/j.ejphar.2021.173974
Ferreira P, Ferrari-Souza JP, Tissot C, et al. Potential utility of plasma P-tau and neurofilament light chain as surrogate biomarkers for preventive clinical trials. Neurology. 2023;101:38-45. DOI: https://doi.org/10.1212/WNL.0000000000207115
Rauchmann BS, Schneider-Axmann T, Perneczky R. Associations of longitudinal plasma p-tau181 and NfL with tau-PET, Aβ-PET and cognition. J Neurol Neurosurg Psychiatry. 2021;92:1289-1295. DOI: https://doi.org/10.1136/jnnp-2020-325537
Truffi M, Garofalo M, Ricciardi A, et al. Neurofilament-light chain quantification by Simoa and Ella in plasma from patients with dementia: a comparative study. Sci Rep. 2023;13:4041. DOI: https://doi.org/10.1038/s41598-023-29704-8
Vandenberghe R, Rinne JO, Boada M, et al. Bapineuzumab for mild to moderate Alzheimer's disease in two global, randomized, phase 3 trials. Alzheimers Res Ther. 2016;8:18. DOI: https://doi.org/10.1186/s13195-016-0189-7
Doody RS, Thomas RG, Farlow M, et al. Phase 3 trials of solanezumab for mild-to-moderate Alzheimer's disease. N Engl J Med. 2014;370:311-321. DOI: https://doi.org/10.1056/NEJMoa1312889
Sevigny J, Chiao P, Bussière T, et al. The antibody aducanumab reduces Abeta plaques in Alzheimer's disease. Nature. 2016;537:50-56. DOI: https://doi.org/10.1038/nature19323
FDA. FDA Grants Accelerated Approval for Alzheimer's Drug. FDA; 2021. Accessed September 10, 2023. https://www.fda.gov/newsevents/press-announcements/fda-grants-accelerated-approvalalzheimers-drug .
U.S. Food & Drug Administration. Drugs@FDA: FDA-Approved Drugs. Aducanumab. Reference ID 4822820 2021
EMA. Aduhelm: Withdrawal of the Marketing Authorisation Application. EMA; 2022. Accessed September 10, 2023. https:// www.eisai.com/news/2022/news202271.html
Nilsberth C, Westlind-Danielsson A, Eckman CB, et al. The ‘Arctic’ APP mutation (E693G) causes Alzheimer's disease by enhanced Abeta protofibril formation. Nat Neurosci. 2001;4:887-893. DOI: https://doi.org/10.1038/nn0901-887
Lord A, Gumucio A, Englund H, et al. An amyloid-beta protofibrilselective antibody prevents amyloid formation in a mouse model of Alzheimer's disease. Neurobiol Dis. 2009;36:425-434. DOI: https://doi.org/10.1016/j.nbd.2009.08.007
EISAI. Lecanemab confirmatory phase 3 Clarity AD study met primary endpoint, showing highly statistically significant reduction of clinical decline in large global clinical study of 1,795 participants with early Alzheimer's disease. EISAI; 2022. Accessed September 10, 2023.
van Dyck CH, Swanson CJ, Aisen P, et al. Lecanemab in early Alzheimer's disease. N Engl J Med. 2022;388:9-21. DOI: https://doi.org/10.1056/NEJMoa2212948
Piller C. Scientists tie third clinical trial death to experimental Alzheimer's drug. Science. 2022. Accessed September 10, 2023.
FDA Grants Accelerated Approval for Alzheimer's Disease Treatment. FDA; 2023. Accessed September 10, 2023. https:// www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-alzheimers-disease-treatment.
Ostrowitzki S, Lasser RA, Dorflinger E, et al. A phase III randomized trial of gantenerumab in prodromal Alzheimer's disease. Alzheimers Res Ther. 2017;9:95. DOI: https://doi.org/10.1186/s13195-017-0318-y
Genentech. Genentech Provides Update on Phase III GRADUATE Program Evaluating Gantenerumab in Early Alzheimer's Disease. Genentech; 2022. Accessed September 10, 2023. https://www. gene.com/media/press-releases/14974/2022-11-13/genentechprovides-update-on-phase-iii-g
Mintun MA, Lo AC, Duggan Evans C, et al. Donanemab in early Alzheimer's disease. N Engl J Med. 2021;384:1691-1704. DOI: https://doi.org/10.1056/NEJMoa2100708
Downloads
Published
Issue
Section
License
Copyright (c) 2024 International Journal of Scientific Research in Science and Technology
This work is licensed under a Creative Commons Attribution 4.0 International License.
How to Cite
